Introduction
Prostate-Specific Antigen (PSA) screening in men over the age of 70 has become increasingly controversial. Influential guidelines, including those from the U.S. Preventive Services Task Force, discourage routine PSA testing in this population due to the high risk of overdiagnosis and overtreatment¹. The rationale is that most prostate cancers in older men are slow-growing and unlikely to affect mortality and that interventions often lead to more harm than benefit².
However, this reasoning rests on a critical—and potentially dangerous—assumption: that prostate enlargement is a benign, inconsequential part of aging. In reality, benign prostatic hyperplasia (BPH) may be neither benign nor inconsequential. It reflects a deeper endocrine dysfunction that, if left unaddressed, can create the very hormonal environment that promotes malignancy³⁻⁵. A recent, high-profile example highlights the stakes of this oversight.
The Biden Case: A Wake-Up Call
In early 2025, President Joe Biden, then 82 years old, was diagnosed with an aggressive form of prostate cancer with a Gleason score of 9, indicating a high-grade, rapidly advancing tumor. Notably, Biden had not undergone PSA screening since 2014. His cancer was only discovered after he developed urinary symptoms that prompted further investigation. By the time of diagnosis, the cancer had already metastasized to bone⁹.
This case exposes a dangerous flaw in current guidelines: by withholding PSA screening solely based on age, clinicians risk missing aggressive, life-threatening cancers in men who are otherwise healthy and could benefit from early intervention. It also raises the question: What if we had looked deeper, earlier—not just at PSA, but at the underlying hormonal terrain driving prostate changes?
Thesis
This paper argues that the conventional rationale for avoiding PSA testing in older men is predicated on a false sense of security: that prostate enlargement is harmless. In fact, BPH is often a symptom of hormonal imbalance, particularly the accumulation of unopposed estrogen and heightened sensitivity to dihydrotestosterone (DHT)³⁻⁵. Ignoring this early signal forfeits the chance to intervene at a reversible stage, before malignant transformation occurs. Rather than abandoning screening, we should expand it to include hormonal profiling that reflects the true drivers of prostate pathology.
The Flawed Assumption of “Benign” Enlargement
Benign prostatic hyperplasia is typically framed as a non-threatening, age-related change, an unavoidable part of male aging. Yet the symptoms of BPH (urinary retention, waking up to urinate, frequency) suggest a highly active biological process. Research increasingly shows that this “benign” growth is mediated by hormonal signaling, inflammation and cellular remodeling, not passive aging³⁻⁵.
Despite this, the medical system often dismisses elevated PSA as merely a reflection of BPH. Biopsy is avoided, cancer is “ruled out,” and no further investigation is pursued. But if the enlargement itself is hormonally driven and the hormonal environment is conducive to cellular proliferation, this passivity may be precisely what allows malignancy to take root.
The Hormonal Terrain of the Aging Male
Men do not simply “run out” of testosterone with age. Instead, the aging process alters hormonal balance: testosterone declines while aromatase activity increases, leading to a relative rise in estradiol⁶. Compounding this, serum hormone panels typically test for total testosterone and estrogen, ignoring the free, bioavailable fractions that directly affect tissue.
Elevated estradiol, especially unopposed by adequate testosterone, has been shown to increase androgen receptor expression in prostate cells, sensitizing the prostate to DHT³⁻⁵. Even normal levels of DHT, in this altered hormonal landscape, can promote hypertrophy, inflammation and eventually oncogenesis. See Fig 1.
Estrogen-DHT Synergy and Missed Opportunities
Studies have shown that the combination of estrogen and DHT promotes more aggressive prostate growth than either hormone alone³⁻⁵. Despite this, men are rarely screened for estrogen levels, let alone the free fractions that exert biological effects. Functional medicine and endocrinology have recognized this for decades, yet it remains absent from mainstream urology.
If men like Joe Biden had received regular hormonal assessments, tracking not only PSA, but also estradiol, testosterone, DHT and SHBG, interventions could have been made early. Nutritional, lifestyle, or pharmaceutical modulation of these hormone levels might have prevented or delayed the onset of aggressive disease.
BPH as an Entropic Marker, Not a Harmless Side Effect
The dismissal of prostate enlargement as “benign” rests not only on pathology reports but on flawed assumptions about aging itself. Many clinicians justify ignoring elevated PSA or prostate-related symptoms in older men because “something else will likely kill them first.” This logic dangerously conflates late-life onset with low clinical significance.
But morbidity, not just mortality, defines healthspan. By the time BPH results in chronic urinary symptoms, inflammation, or recurrent infections, it’s already signaling multi-system failure: hormonal imbalances, immune dysregulation and mitochondrial decline⁷. These are all hallmarks of rising biological entropy.
BPH is not a standalone diagnosis, it is a visible marker of accelerated systemic decay. Treating it as trivial because it appears late is a profound misreading of the aging process. In fact, the timing of BPH may be a final warning, not an excuse for inaction.
Rethinking PSA: From Diagnosis to Early Warning
Rather than viewing PSA as a flawed cancer detection tool, we should reinterpret it as a biological barometer of hormonal activity and inflammatory response. Elevated PSA in the context of BPH should trigger hormonal evaluation, not dismissal. It is a chance to address a system in flux before pathology becomes irreversible.
The alternative—foregoing testing entirely in older men—essentially gambles that any cancer that develops will be slow and insignificant. As the Biden case illustrates, this is not always true⁹.
Time to Redefine “Benign”
The argument against PSA screening in older men collapses if the premise of benign prostate growth is incorrect. BPH is not harmless; it is hormonally driven and potentially preventable. Elevated estrogen, unchecked DHT activity and declining testosterone create a high-risk environment for uncontrolled prostate growth and possibly cancer.
Rather than limit screening based on age, we should expand our diagnostic lens. Incorporating hormonal testing into the assessment of prostate health allows for earlier, less invasive interventions that can preserve quality of life and perhaps save it.
References
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Available from: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prostate-cancer-screening
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Available from: https://doi.org/10.1016/j.cell.2013.05.039
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